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    Exudates from <em>Miscanthus</em> x <em>giganteus</em> change the response of a root-associated <em>Pseudomonas</em> <em>putida</em> strain towards heavy metals.

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    The composition of root exudates is modulated by several environmental factors, and it remains unclear how that affects beneficial rhizosphere or inoculated microorganisms under heavy metal (HM) contamination. Therefore, we evaluated the transcriptional response of Pseudomonas putida E36 (a Miscanthus x giganteus isolate with plant growth promotion-related properties) to Cd, Pb and Zn in an in vitro study implementing root exudates from M. x giganteus. To collect root exudates and analyse their composition plants were grown in a pot experiment under HM and control conditions. Our results indicated higher exudation rate for plants challenged with HM. Further, out of 29 organic acids identified and quantified in the root exudates, 8 of them were significantly influenced by HM (e.g., salicylic and terephthalic acid). The transcriptional response of P. putida E36 was significantly affected by the HM addition to the growth medium, increasing the expression of several efflux pumps and stress response-related functional units. The additional supplementation of the growth medium with root exudates from HM-challenged plants resulted in a downregulation of 29% of the functional units upregulated in P. putida E36 as a result of HM addition to the growth medium. Surprisingly, root exudates&nbsp;+&nbsp;HM downregulated the expression of P. putida E36 functional units related to plant colonization (e.g., chemotaxis, motility, biofilm formation) but upregulated its antibiotic and biocide resistance compared to the control treatment without HM. Our findings suggest that HM-induced changes in root exudation pattern may attract beneficial bacteria that are in turn awarded with organic nutrients, helping them cope with HM stress. However, it might affect the ability of these bacteria to colonize plants growing in HM polluted areas. Those findings may offer an insight for future in vivo studies contributing to improvements in phytoremediation measures

    Long term exposure to air pollution and kidney parenchyma cancer – Effects of low-level air pollution: A Study in Europe (ELAPSE).

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    BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited. METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: The participants were followed from baseline (1985–2005) to 2011–2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5–95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 μg/m3 (12.8–39.2), 15.3 μg/m3 (8.6–19.2), 1.6 10−5 m−1 (0.7–2.1), and 87.0 μg/m3 (70.3–97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 μg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10−5 m−1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 μg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma. CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer

    Tracing long-distance electron transfer and cable bacteria in freshwater sediments by agar pillar gradient columns.

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    Cable bacteria (CB) perform electrogenic sulphur oxidation (e-SOX) by spatially separating redox-half-reactions over cm-distances. For freshwater systems, the ecology of CB is not yet well understood, partly because they proved difficult to cultivate. This study introduces a new "agar pillar" approach to selectively enrich and investigate CB-populations. Within sediment columns, a central agar pillar is embedded, providing a sediment-free gradient-system in equilibrium with the surrounding sediment. We incubated freshwater sediments from a streambed, a sulfidic lake, and a hydrocarbon polluted aquifer in such agar pillar columns. Microprofiling revealed typical patterns of e-SOx, such as the development of a suboxic zone and the establishment of electric potentials. The bacterial communities in the sediments and agar pillars were analysed over depth by PacBio near-full-length 16S rRNA gene amplicon sequencing, allowing for a precise phylogenetic placement of taxa detected. The selective niche of the agar pillar was preferentially colonized by CB related to Candidatus Electronema for surface-water sediments, including several potentially novel species, but not for putative groundwater CB affiliated with Desulfurivibrio spp. The presence of CB was seemingly linked to co-enriched fermenters, hinting at a possible role of e-SOx-populations as an electron sink for heterotrophic microbes. These findings add to our current understanding of the diversity and ecology of CB in freshwater systems, and to a discrimination of CB from surface and groundwater sediments. The agar pillar approach provides a new strategy that may facilitate the cultivation of redox gradient-dependent microorganisms, including previously unrecognized CB populations

    Clinical validation of saliency maps for understanding deep neural networks in ophthalmology.

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    Deep neural networks (DNNs) have achieved physician-level accuracy on many imaging-based medical diagnostic tasks, for example classification of retinal images in ophthalmology. However, their decision mechanisms are often considered impenetrable leading to a lack of trust by clinicians and patients. To alleviate this issue, a range of explanation methods have been proposed to expose the inner workings of DNNs leading to their decisions. For imaging-based tasks, this is often achieved via saliency maps. The quality of these maps are typically evaluated via perturbation analysis without experts involved. To facilitate the adoption and success of such automated systems, however, it is crucial to validate saliency maps against clinicians. In this study, we used three different network architectures and developed ensembles of DNNs to detect diabetic retinopathy and neovascular age-related macular degeneration from retinal fundus images and optical coherence tomography scans, respectively. We used a variety of explanation methods and obtained a comprehensive set of saliency maps for explaining the ensemble-based diagnostic decisions. Then, we systematically validated saliency maps against clinicians through two main analyses — a direct comparison of saliency maps with the expert annotations of disease-specific pathologies and perturbation analyses using also expert annotations as saliency maps. We found the choice of DNN architecture and explanation method to significantly influence the quality of saliency maps. Guided Backprop showed consistently good performance across disease scenarios and DNN architectures, suggesting that it provides a suitable starting point for explaining the decisions of DNNs on retinal images

    Levels and drivers of urban black carbon and health risk assessment during pre- and COVID19 lockdown in Augsburg, Germany.

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    This study aimed to evaluate the levels and phenomenology of equivalent black carbon (eBC) at the city center of Augsburg, Germany (01/2018 to 12/2020). Furthermore, the potential health risk of eBC based on equivalent numbers of passively smoked cigarettes (PSC) was also evaluated, with special emphasis on the impact caused by the COVID19 lockdown restriction measures. As it could be expected, peak concentrations of eBC were commonly recorded in morning (06:00–8:00 LT) and night (19:00–22:00 LT) in all seasons, coinciding with traffic rush hours and atmospheric stagnation. The variability of eBC was highly influenced by diurnal variations in traffic and meteorology (air temperature (T), mixing-layer height (MLH), wind speed (WS)) across days and seasons. Furthermore, a marked “weekend effect” was evidenced, with an average eBC decrease of ∼35% due to lower traffic flow. During the COVID19 lockdown period, an average ∼60% reduction of the traffic flow resulted in ∼30% eBC decrease, as the health risks of eBC exposure was markedly reduced during this period. The implementation of a multilinear regression analysis allowed to explain for 53% of the variability in measured eBC, indicating that the several factors (e.g., traffic and meteorology) may contribute simultaneously to this proportion. Overall, this study will provide valuable input to the policy makers to mitigate eBC pollutant and its adverse effect on environment and human health

    Health, pleasure, and fullness: changing mindset affects brain responses and portion size selection in adults with overweight and obesity.

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    Background Increased portion size is an essential contributor to the current obesity epidemic. The decision of how much to eat before a meal begins (i.e. pre-meal planning), and the attention assigned to this task, plays a vital role in our portion control. Objective We investigated whether pre-meal planning can be influenced by a shift in mindset in individuals with overweight and obesity in order to influence portion size selection and brain activity. Design We investigated the neural underpinnings of pre-meal planning in 36 adults of different weight groups (BMI &lt; 25 kg/m(2) and BMI &gt;= 25 kg/m(2)) by means of functional magnetic resonance imaging. To examine the important role of attentional focus, participants were instructed to focus their mindset on the health effects of food, expected pleasure, or their intention to stay full until dinnertime, while choosing their portion size for lunch. Results We observed that participants of all weight groups reduced their portion size when adopting a health mindset, which was accompanied by enhanced activation of the self-control network (i.e. left prefrontal cortex). Fullness and pleasure mindsets resulted in contrasting reward responses in individuals with overweight and obesity compared to normal-weight individuals. Under the pleasure mindset, persons with overweight and obesity showed heightened activity in parts of the taste cortex (i.e. right frontal operculum), while the fullness mindset caused reduced activation in the ventral striatum, an important component of the reward system. Moreover, participants with overweight and obesity did not modify their behaviour under the pleasure mindset and selected larger portions than the normal-weight group. Conclusions We were able to identify specific brain response patterns as participants made a final choice of a portion size. The results demonstrate that different brain responses and behaviours during pre-meal planning can inform the development of effective strategies for healthy weight management

    Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis.

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    Ferroptosis is a druggable, iron-dependent form of cell death that is characterized by lipid peroxidation but has received little attention in lupus nephritis. Kidneys of lupus nephritis patients and mice showed increased lipid peroxidation mainly in the tubular segments and an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme. Nephritic mice had an attenuated expression of SLC7A11, a cystine importer, an impaired glutathione synthesis pathway, and low expression of glutathione peroxidase 4, a ferroptosis inhibitor. Lipidomics of nephritic kidneys confirmed ferroptosis. Using nephrotoxic serum, we induced immune complex glomerulonephritis in congenic mice and demonstrate that impaired iron sequestration within the proximal tubules exacerbates ferroptosis. Lupus nephritis patient serum rendered human proximal tubular cells susceptibility to ferroptosis which was inhibited by Liproxstatin-2, a novel ferroptosis inhibitor. Collectively, our findings identify intra-renal ferroptosis as a pathological feature and contributor to tubular injury in human and murine lupus nephritis

    Design and characterization of dietary assessment in the German National Cohort.

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    Background/Objectives The aim of the study was to describe a novel dietary assessment strategy based on two instruments complemented by information from an external population applied to estimate usual food intake in the large-scale multicenter German National Cohort (GNC). As proof of concept, we applied the assessment strategy to data from a pretest study (2012-2013) to assess the feasibility of the novel assessment strategy.Subjects/Methods First, the consumption probability for each individual was modeled using three 24 h food lists (24h-FLs) and frequencies from one food frequency questionnaire (FFQ). Second, daily consumed food amounts were estimated from the representative German National Nutrition Survey II (NVS II) taking the characteristics of the participants into account. Usual food intake was estimated using the product of consumption probability and amounts.Results We estimated usual intake of 41 food groups in 318 men and 377 women. The participation proportion was 100, 84.4, and 68.5% for the first, second, and third 24h-FL, respectively. We observed no associations between the probability of participating and lifestyle factors. The estimated distributions of usual food intakes were plausible and total energy was estimated to be 2707 kcal/day for men and 2103 kcal/day for women. The estimated consumption frequencies did not differ substantially between men and women with only few exceptions. The differences in energy intake between men and women were mostly due to differences in estimated daily amounts.Conclusions The combination of repeated 24h-FLs, a FFQ, and consumption-day amounts from a reference population represents a user-friendly dietary assessment approach having generated plausible, but not yet validated, food intake values in the pretest study

    The effect of air pollution when modified by temperature on respiratory health outcomes: A systematic review and meta-analysis.

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    Background: Respiratory diseases are a leading cause of mortality and morbidity, and are exacerbated by air pollution and temperature. Aim: To assess published literature on the effect of air pollution modified by temperature on respiratory mortality and hospital admissions. Methods: We identified 26,656 papers in PubMed and Web of Science, up to March 2021, and selected for analysis; inclusion criteria included observational studies, short-term air pollution, and temperature exposure. Air pollutants considered were particulate matter with a diameter of 2.5 μg/m3, and 10 μg/m3 (PM2.5, and PM10), ozone (O3), and nitrogen dioxide (NO2). A random-effects model was used for our meta-analysis. Results: For respiratory mortality we found that when the effect PM10 is modified by high temperatures there is an increased pooled Odds Ratio [OR, 95% Confidence Interval (CI)] of 1.021 (1.008 to 1.034) and for the effect of O3 the pooled OR is 1.006 (1.001–1.012) during the warm season. For hospital admissions, the effects of PM10 and O3 respectively, during the warm season found an increased pooled OR of 1.011 (0.999–1.024), and 1.015 (0.995–1.036). In our analysis for low temperatures, results were inconsistent. Conclusions: Exposure to air pollution when modified by high temperature is likely to increase the odds of respiratory mortality and hospital admissions. Analysis on the interaction effect of air pollution and temperature on health outcomes is a relatively new research field and results are largely inconsistent; therefore, further research is encouraged to establish a more conclusive conclusion on the strength and direction of this effect

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